Field of the Invention
The present disclosure relates to an apparatus for the generation of an animal spinal cord injury model, and more particularly, to an apparatus and method that inflicts spinal cord injury (hereinafter shortened as ‘SCI’) by dropping an impactor in free fall to impact the spinal cord.
Description of the Related Art
Spinal cord injury is caused by trauma such as car, sporting and industrial accidents and non-trauma such as infection, loss of blood supply, tumor and spinal distortion, and common causes are trauma. The symptoms of spinal cord injury include impairment of motor and sensory function. Spinal cord injury often happens in young people because most of spinal cord injuries result from accidents, and neurological recovery in spinal cord injury is not easy compared to peripheral nerve injury, resulting in many types of impairments, so spinal cord injury is catastrophic, affecting loss of economy, emotion and time of the patient and family.
From this perspective, development of treatment methods of spinal cord injury using animals is an essential process for clinical trials, and currently, many types of spinal cord injury models are used in animal testing. After all, spinal cord injury models are an essential process to find the causes of spinal cord injury in humans and develop systematic treatment methods.
Existing spinal cord injury models using animals may be largely classified into two based on the method of injury. One is a transection model of which the spinal cord is transected in part or in whole, and the other is a contusion model of which the spinal cord is damaged by impact of a weight with a defined mass dropped from a preset height. The contusion model is the most commonly occurring injury mechanism in human clinical trials, and is mainly used for study of spinal cord injury mechanisms or assessment of early phases of injury.
Spinal cord injury models may be classified into incomplete spinal cord injury and complete spinal cord injury based on the injury severity. The most common type of spinal cord injury occurring in clinical trials is closed partial contusion injury caused by vertebral burst fracture and spinal disc herniation due to injury, and complete spinal cord injury caused by a transection in the spinal cord is less common. Accordingly, many spinal cord injury experiments use partial contusion injury models, but disadvantages of these injury models are that it is not easy to clearly identify a desired treatment effect due to non-uniform damage severity and relatively high levels of intrinsic recovery ability of the spinal cord, and it is difficult to clearly distinguish regeneration of the damaged axons and nerves from collateral sprouting in the surviving nervous tissue after damage. For a solution to these disadvantages, complete spinal cord injury models may be used.
Conventionally, permanent loss of tissue related to nerve function or nerve regeneration of the spinal cord may occur due to SCI, and in studies of the development of treatments for SCI, investigators have primarily used rodents such as mice or rats in animal testing as shown in FIG. 1.
However, modeling of animals having more similar spinal cords to humans than rodents was needed, and in 2013, Lee, Kwon et al., University of British Columbia in Canada, developed a model of SCI using female Yucatan miniature pig of about 20-25 kg and a spinal cord injuring device (SC impactor) devised by them. The spinal cord injuring apparatus used is as shown in FIG. 2.
The original source of the photographic images of FIGS. 1 and 2 is on http://www.bio-protocol.org/e886 and Lee et al., Journal of Neurotrauma 30:142-159, Feb. 1, 2013.
The apparatus is largely divided into two: a guide member indicated by number 1, and an impactor indicated by number 2 in the left picture of FIG. 2. The guide member is a tool that plays a role in guide the impactor to accurately fall onto the porcine spinal cord, and a solenoid mounted on the guide member rail is the trigger of free fall. Quadrant (marker) attached to the rail is attached to the impactor as well, and they are tracked using a high-speed video camera system and used to calculate the velocity and displacement. The guide member is fixed at the back and abdomen of the animal with pedicle screws. The impactor includes a tip that touches the quadrant (marker) and the spinal cord, and a load cell sensor connected to the tip. Particularly, the high-speed camera is a high-priced device that is an economical burden factor to the system architecture, and the time resolution of physical quantity measurements resulting from impact is limited by low frame rates set at the commonly used image resolution. For example, in the case of Phantom Miro M320S, the device ranges in price from USD 45,000 to 60,000 depending on the elements, and has a maximum frame rate of 3,280 FPS at 1280×720 resolution.
The procedure for SCI experiment using the device is summarized in brief as below. First, after a high speed camera is installed, a guide member is fixed to an anesthetized animal using pedicle screws, and then, an impactor is mounted on a rail of the guide member deployed vertically, and the impactor is moved to a solenoid fixed at a defined height and gets ready to fall. After the condition of the anesthetized animal (the condition of bones, muscles, and tissues) is identified, a trigger signal is given to the solenoid to cause the impactor to drop in free fall to impact the spinal cord, resulting in acute traumatic spinal cord injury. In some cases, to give additional damage to the target spinal cord, the pressure is applied continuously to the spinal cord with the impactor still held for a defined period of time (about 5 minutes) immediately after the fall. The physical quantities related to the impact that can be obtained using the experiment apparatus are peak force, impact velocity, maximum dural displacement, and peak pressure. The peak force is measured using the load cell sensor attached to the impactor, and the impact velocity and the maximum dural displacement are measured by tracking the markers attached to the aforementioned devices using a high-speed video camera system. The peak pressure is measured using the peak force and the area of the cross section of the tip. In this instance, the peak force having dynamic properties does not stay static and sharply changes at impact, and as load cell output signals are limited in bandwidth through a low pass filter for removing noise, there is a likelihood that errors in peak force measurement may occur.
The problems of the conventional impactor system for inflicting SCI on large animals are summarized as below:
1. To implement the apparatus, there are disadvantages; a high-priced high speed video camera is indispensably needed, and complex algorithm software for video system that tracks the motion of the impactor is necessary.
2. Despite using the high-priced video system, errors may occur in physical quantity measurement, such as the impact velocity and the maximum spinal cord indentation depth, rapidly changing due to the high speed camera having a relatively low frame rate.
3. Peak force having dynamic properties does not stay static and sharply changes at impact, and as load cell output signals are limited in bandwidth through a low pass filter for removing noise, there is a likelihood that errors in peak force measurement may occur.
4. Peak force is an instantaneous force applied to the spinal cord, and is unsuitable to typically represent a force applied by an impact for a defined amount of time even though it is a short time.
5. The video system described previously may have varying measured values of the impact velocity and the maximum spinal cord indentation depth depending on the installation location and orientation of the camera, requiring a defined distance from the impactor device and accurate placement.
6. A fixation technique using pedicle screws is an invasive method that may inflict a nerve injury or vascular injury on a fixed site.
Meanwhile, the most important requirement as an experiment model of spinal cord injury is a standardized damage method, and a difference in the degree of recovery between subjects damaged by the same method that is not great and so uniform that a treatment effect between a control group and an experiment group can be clearly distinguished.